RESUMO
In this review we address the main cutaneous manifestations and diseases associated with deficiencies in components of the complement system. The first part is devoted to hereditary angioedema, in which acute, sometimes life-threatening recurrent attacks of acute swelling, usually associated with gastrointestinal symptoms, occur. It is related to a structural or functional deficiency of C1 esterase inhibitor. Patients usually have lowered C4 levels, and diagnosis relies on determination of antigenic and/or functional C1 inhibitor level. The second part focuses on lupus erythematosus, as deficiencies in early components of the complement system, such as C1q, C1r, C1s, C2 or C4, are the strongest known disease susceptibility genes for the development of human systemic lupus erythematosus. Severe infections early in life and marked photosensitivity in a patient with lupus erythematosus are clues to an underlying complement deficiency. The genetic background and the clinical associations of the different components of the complement system will be detailed.
Assuntos
Proteínas do Sistema Complemento/deficiência , Lúpus Eritematoso Sistêmico/genética , Dermatopatias/etiologia , Complemento C1/deficiência , Complemento C1/genética , Complemento C2/efeitos dos fármacos , Complemento C2/genética , Complemento C4/efeitos dos fármacos , Complemento C4/genética , Proteínas do Sistema Complemento/genética , Predisposição Genética para Doença , Humanos , Transtornos de Fotossensibilidade/diagnóstico , Transtornos de Fotossensibilidade/etiologia , Dermatopatias/patologiaRESUMO
Complete deficiency of complement C4 is among the strongest genetic risk factors for human systemic lupus erythematosus (SLE). C4 is a constituent of the RP-C4-CYP21-TNX (RCCX) module in the human leukocyte antigen (HLA) that exhibits inter-individual copy-number and gene-size variations. Here, we studied two North-African families with complete C4 deficiency and SLE. The first included a Moroccan male SLE patient (1P) and a sibling, who were both homozygous for HLA-A*02 B*17 DRB1*07. The second had an Algerian female SLE patient (2P) homozygous for HLA-A*01 B*17 DRB1*13. Early SLE disease onset, the presence of photosensitive rashes, anti-Ro/SSA, renal disease and high titers of antinuclear antibodies were the common features of complete C4 deficiency. Southern blot analyses showed that 1P had monomodular RCCX with a long C4A, whereas 2P had bimodular RCCX with one long C4A and one short C4B. Genomic DNA fragments for these mutant genes were amplified and sequenced. A C>T transition that created the R540X nonsense mutation in C4A was found in 1P. An identical 4-bp insertion that generated the Y1537X nonsense mutation was discovered in both C4A and C4B of 2P. The high concordance of SLE and C4 deficiency among patients with non-DR3 and non-DR2 haplotypes underscores the importance of C4 proteins in the protection against SLE.
Assuntos
Complemento C4/deficiência , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/imunologia , População Negra/genética , Complemento C4/genética , Complemento C4/imunologia , Consanguinidade , Feminino , Antígenos HLA-A/genética , Humanos , Masculino , LinhagemRESUMO
INTRODUCTION: Deficiencies in components of the classical pathway of complement activation are strong risk factors for lupus erythematosus (LE).Yet, it has not been addressed whether the conventional measurements of the serum hemolytic CH50 activity and antigenic concentrations of C3 and C4 are sufficient to asses a deficiency in C4A, C4B or C2 components, the most common deficiencies associated with LE. PATIENTS AND METHODS: In a retrospective series, we performed complement analyses in 35 patients with LE who were systematically screened for a complement deficiency. The majority of patients had cutaneous LE with mild systemic involvement and no complement consumption. Of 25 patients (72%) with complement deficiency we found 13 with a partial C4A deficiency, 2 with a complete C4A deficiency, 6 with a partial C4B deficiency, 2 with a complete C4B deficiency and 2 with a combined partial C2 and C4A deficiency. RESULTS: The total complement activity (CH50) was decreased in only one out of two patients with complete C4B deficiency. CH50 level was found to be low-normal (35-38 U/ml(-1)) in one patient with partial C4B deficiency, one patient with complete C4B deficiency and both patients with combined partial C4A and C2 deficiency. Total C4 levels were normal in 9 out of 13 the patients with a partial C4A deficiency and in 2 out of 6 patients with a complete C4B deficiency. The antigenic concentration of C3 was low in only 1 patients with a complete C4B deficiency and within the normal range in all the others patients. Overall, 50% of the patients had normal or elevated C3, C4, and CH50 levels. DISCUSSION: This study emphasizes that the usual measurements of CH50, C3 and C4 levels are not adequate to detect a C4 and/or C2 deficiency in patients with LE. In epidemiologic or investigative studies addressing the prevalence of complement deficiency, more elaborated diagnostic tests, such as C4 protein allotyping, C2 level measurement and genetic screening for type I C2 deficiency should also be performed.
Assuntos
Complemento C3/deficiência , Complemento C4/deficiência , Ensaio de Atividade Hemolítica de Complemento/métodos , Proteínas do Sistema Complemento/deficiência , Lúpus Eritematoso Sistêmico/imunologia , Adulto , Complemento C3/análise , Complemento C4/análise , Proteínas do Sistema Complemento/análise , Feminino , Variação Genética , Antígenos de Histocompatibilidade/análise , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Estudos RetrospectivosRESUMO
BACKGROUND: Although deficiencies in the early components of the complement system were among the first identified genetic risk factors for systemic lupus erythematosus (SLE), only a few studies addressed their significance in patients with cutaneous LE (CLE). Among environmental factors, it was postulated that cigarette smoking might intervene in the pathogenesis of LE. OBJECTIVES: To describe the clinical and biological features of patients with CLE and a complement deficiency. A secondary objective was to assess cigarette smoking in patients with CLE. PATIENTS AND METHODS: A retrospective study including all patients diagnosed as having LE between 1995 and 2003 in the Dermatology Department of Strasbourg University Hospital. Patient charts were reviewed and those patients in whom a C4 and/or C2 deficiency was diagnosed were included. Two patients with a combined C2/C4 deficiency were analysed in detail. RESULTS: There were 48 females and 37 males (F/M ratio = 1.3), with a mean age of 41 years at diagnosis; 73% of the patients had chronic LE and 27% subacute CLE. Among 32 screened patients, 24 patients with a mean age of 36 years had a complement deficiency; 17 had a C4A deficiency, five a C4B deficiency and two a combined C4A/C2 deficiency. A high proportion (58%) of these patients was male; 82% of the patients were smokers. This was especially true in males: 94% were smokers compared with 69% of females. CONCLUSIONS: Partial deficiency of C4, C2 or C4 and C2 is a common finding in patients with CLE. Most male patients with CLE are smokers. It is thus suggested that the combination of cigarette smoking and complement deficiency could be a risk factor for LE in men.
Assuntos
Complemento C2/deficiência , Complemento C4/deficiência , Lúpus Eritematoso Cutâneo/etiologia , Fumar/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Lúpus Eritematoso Cutâneo/imunologia , Lúpus Eritematoso Cutâneo/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
The vertebrate midbrain-hindbrain boundary (MHB) organizes patterning and neuronal differentiation in the midbrain and anterior hindbrain. Formation of this organizing center involves multiple steps, including positioning of the MHB within the neural plate, establishment of the organizer and maintenance of its regional identity and signaling activities. Juxtaposition of the Otx2 and Gbx2 expression domains positions the MHB. How the positional information is translated into activation of Pax2, Wnt1 and Fgf8 expression during MHB establishment remains unclear. In zebrafish spiel ohne grenzen (spg) mutants, the MHB is not established, neither isthmus nor cerebellum form, the midbrain is reduced in size and patterning abnormalities develop within the hindbrain. In spg mutants, despite apparently normal expression of otx2, gbx1 and fgf8 during late gastrula stages, the initial expression of pax2.1, wnt1 and eng2, as well as later expression of fgf8 in the MHB primordium are reduced. We show that spg mutants have lesions in pou2, which encodes a POU-domain transcription factor. Maternal pou2 transcripts are distributed evenly in the blastula, and zygotic expression domains include the midbrain and hindbrain primordia during late gastrulation. Microinjection of pou2 mRNA can rescue pax2.1 and wnt1 expression in the MHB of spg/pou2 mutants without inducing ectopic expression. This indicates an essential but permissive role for pou2 during MHB establishment. pou2 is expressed normally in noi/pax2.1 and ace/fgf8 zebrafish mutants, which also form no MHB. Thus, expression of pou2 does not depend on fgf8 and pax2.1. Our data suggest that pou2 is required for the establishment of the normal expression domains of wnt1 and pax2.1 in the MHB primordium.
Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Mesencéfalo/embriologia , Proteínas Nucleares , Rombencéfalo/embriologia , Fatores de Transcrição/genética , Proteínas de Peixe-Zebra , Peixe-Zebra/embriologia , Animais , Proteínas de Ligação a DNA/genética , Embrião não Mamífero , Feminino , Fator 8 de Crescimento de Fibroblasto , Fatores de Crescimento de Fibroblastos/genética , Gástrula , Proteínas de Homeodomínio/genética , Mutação , Proteínas do Tecido Nervoso/genética , Fator 3 de Transcrição de Octâmero , Organizadores Embrionários , Fatores de Transcrição Otx , Fator de Transcrição PAX2 , Fator de Transcrição PAX5 , Fator de Transcrição PAX8 , Fatores de Transcrição Box Pareados , Proteínas , Proteínas Proto-Oncogênicas/genética , Transativadores/genética , Fatores de Transcrição/metabolismo , Proteínas Wnt , Proteína Wnt1 , Peixe-Zebra/genéticaRESUMO
This article contains detailed protocols for the localization of mRNA transcripts within whole Drosophila embryos. The procedures are based on the use of digoxigenin-, fluorescein-, and biotin-labeled antisense RNA probes for nonradioactive detection of transcripts. The labels are visualized in situ by differently colored water-insoluble precipitates using alkaline phosphatase- or beta-galactosidase-based immunoassays. First, a basic method is described that allows detection of transcript distribution(s) of one or more genes using the same color precipitate. Second, a sequential alkaline phosphatase detection method is presented that permits the visualization of two or three independent transcript patterns in multiple colors in the same embryo. Third, a shortened two-color in situ hybridization protocol is provided that employs a combination of beta-galactosidase and alkaline phosphatase colorimetric reactions for differential detection. The two-color in situ hybridization methods work equally well in Drosophila and zebrafish embryos and may therefore also be adaptable to other species.
Assuntos
Embrião não Mamífero/metabolismo , Hibridização In Situ/métodos , Fosfatase Alcalina/metabolismo , Animais , Biotina/farmacologia , Digoxigenina/farmacologia , Drosophila , Sondas Moleculares/farmacologia , RNA Mensageiro/metabolismo , beta-Galactosidase/metabolismoRESUMO
BACKGROUND: The gene deletion responsible for the type I human complement C2 deficiency was reported in 1992. The purpose of our study is to evaluate clinical and immunological characteristics of 11 patients with lupus erythematosus and type I C2 deficiency. OBSERVATIONS: We observed 5 patients with a homozygous C2 deficiency and 6 with a heterozygous C2 deficiency. Eight patients had systemic lupus erythematosus, 2 had subacute cutaneous lupus erythematosus, and 1 had chronic lupus erythematosus. Photosensitivity was present in 73% of the patients, and 64% tested positive for anti-Ro (SSA) antibodies. Renal involvement that required immunosuppressive therapy was present in 54% of the patients. Ninety percent of the patients tested positive for antinuclear antibodies, and 54% tested positive for anti-double-stranded DNA antibodies. Phenotyping of the fourth component of the complement was performed in 82% of the patients and showed a C4A4B2 phenotype, which is suggestive for the type I C2 deficiency. CONCLUSIONS: Most patients with lupus erythematosus associated with C2 type I deficiency are photosensitive, and this is probably related to the presence of anti-Ro (SSA) autoantibodies. The prognosis for those patients is not better than that for patients with lupus erythematosus in general.
Assuntos
Complemento C2/deficiência , Lúpus Eritematoso Sistêmico/genética , Adolescente , Adulto , Primers do DNA , Feminino , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/patologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Reação em Cadeia da Polimerase , Estudos RetrospectivosAssuntos
Embrião não Mamífero/fisiologia , Expressão Gênica , Hibridização In Situ/métodos , Transcrição Gênica , Animais , Corantes , Drosophila/embriologia , Drosophila/genética , Embrião de Mamíferos/citologia , Embrião de Mamíferos/fisiologia , Embrião não Mamífero/citologia , Técnicas de Preparação Histocitológica , Indicadores e Reagentes , Sondas RNA , Peixe-Zebra/embriologia , Peixe-Zebra/genéticaRESUMO
Vertebrate class III POU genes are widely expressed in the embryonic and adult central nervous system, where they act as transcriptional regulators of cell- and/or region-specific gene expression. We isolated four zebrafish class III POU genes, named zp-12, zp-23, zp-47 and zp-50. In this study, we examined the developmental expression patterns of the Brn-1- and Brn-2-related zp-12, zp-23 and zp-47 genes by means of whole-mount in situ hybridization. Similarly to their mammalian orthologues, the major expression site of all zebrafish zp genes is the CNS. Neurectodermal expression was first detected at the beginning of somitogenesis in spatially restricted segment-like domains in different parts of the neural plate. During somitogenesis transcript distributions changed from highly restricted to widespread but nevertheless distinct patterns found in all major subdivisions of the CNS. While zp-47 expression was detected exclusively in the CNS, localized expression of zp-12 and zp-23 was also found in the pronephric primordium and in cell clusters within the mandibular and hyoid arches. Furthermore, zp-23 transcripts were transiently detected in a restricted region of the paraxial mesendoderm and, at late embryogenesis stages, in the auditory vesicles. The early regionalized expression of all three zp genes is compatible with roles in regional specification of the neural plate. Comparison of the distinct yet overlapping expression of zp-12, zp-23, zp-47 and the previously characterized zp-50 gene implies both unique, as well as redundant functions for each family member. We propose that coordinate expression of particular combinations of class III POU genes contribute to pattern formation or cell fate determination in the developing CNS and other structures.
Assuntos
Proteínas de Ligação a DNA/genética , Neuropeptídeos/genética , Transativadores/genética , Fatores de Transcrição/genética , Animais , Encéfalo/embriologia , Encéfalo/metabolismo , Região Branquial/embriologia , Região Branquial/metabolismo , Sistema Nervoso Central/embriologia , Sistema Nervoso Central/metabolismo , Expressão Gênica , Proteínas de Homeodomínio , Rim/embriologia , Rim/metabolismo , Proteínas do Tecido Nervoso , Fatores do Domínio POU , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Proteínas de Peixe-ZebraRESUMO
To shed light on the organization of the rostral embryonic brain of a lower vertebrate, we have directly compared the expression patterns of dlx, fgf, hh, hlx, otx, pax, POU, winged helix and wnt gene family members in the fore- and midbrain of the zebrafish. We show that the analyzed genes are expressed in distinct transverse and longitudinal domains and share expression boundaries at stereotypic positions within the fore- and midbrain. Some of these shared expression boundaries coincide with morphological landmarks like the pathways of primary axon tracts. We identified a series of eight transverse diencephalic domains suggestive of neuromeric subdivisions within the rostral brain. In addition, we identified four molecularly distinct longitudinal subdivisions and provide evidence for a strong bending of the longitudinal rostral brain axis at the cephalic flexure. Our data suggest a strong conservation of early forebrain organization between lower and higher vertebrates.
Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Prosencéfalo/embriologia , Proteínas de Peixe-Zebra , Peixe-Zebra/embriologia , Animais , Vértebra Cervical Áxis , Padronização Corporal , Proteínas do Citoesqueleto , Proteínas de Ligação a DNA/genética , Proteínas do Olho , Proteínas Hedgehog , Proteínas de Homeodomínio/genética , Proteínas do Tecido Nervoso/genética , Fatores de Transcrição Otx , Fator de Transcrição PAX2 , Fator de Transcrição PAX6 , Fatores do Domínio POU , Fatores de Transcrição Box Pareados , Proteínas/genética , Proteínas de Ligação a RNA , Proteínas Repressoras , Transativadores/genética , Fatores de Transcrição/genéticaRESUMO
Properdin deficiency was demonstrated in three generations of a large Swiss family. The concentration of circulating properdin in affected males was < 0.1 mg/l, indicating properdin deficiency type I. Two of the nine properdin-deficient males in the family had survived meningitis caused by Neisseria meningitidis serogroup B without sequel. Two point mutations were identified when the properdin gene in one of the properdin-deficient individuals was investigated by direct solid-phase sequencing of overlapping polymerase chain reaction (PCR) products. The critical mutation was found at base 2061 in exon 4, where the change of cytosine to thymine had generated the stop codon TGA. The other mutation was positioned at base 827 in intron 3. The stop codon in exon 4 was also demonstrated by standard dideoxy sequencing in three additional family members. The question was asked if genetic factors such as partial C4 deficiency and IgG allotypes could have influenced susceptibility to meningococcal disease in the family. No relationship was found between C4 phenotypes and infection. Interestingly, the two properdin-deficient males with meningitis differed from the other properdin-deficient persons in that they lacked the G2m(n) allotype, a marker known to be associated with poor antibody responses to T-independent antigens. This implies that the consequences of properdin deficiency might partly be determined by independent factors influencing the immune response.
Assuntos
Códon de Terminação/genética , Alótipos Gm de Imunoglobulina/genética , Meningite Meningocócica/genética , Properdina/deficiência , Properdina/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Ativação do Complemento/genética , Complemento C4/genética , Feminino , Humanos , Masculino , Meningite Meningocócica/imunologia , Pessoa de Meia-Idade , Linhagem , Polimorfismo Genético/genética , Análise de Sequência de DNA , SuíçaRESUMO
A fast and simplified two-color in situ hybridization procedure for the simultaneous detection of two different mRNAs in whole-mounted zebrafish and Drosophila embryos is presented. Transcript distributions are detected in a single incubation step using a mixture of alkaline phosphatase and beta-galactosidase coupled antibodies. The different transcripts are visualized in contrasting colors by the use of beta-galactosidase substrates that develop color precipitates (magenta, blue) easily distinguishable from those of the standard alkaline phosphatase substrates. This protocol can be followed by standard immunohistochemistry to detect the expression of a third gene (at the protein level) in a third color.
Assuntos
Fosfatase Alcalina/imunologia , Drosophila/embriologia , Peixes/embriologia , RNA Mensageiro/genética , beta-Galactosidase/imunologia , Animais , Embrião não Mamífero/metabolismo , Imuno-Histoquímica , Hibridização de Ácido NucleicoRESUMO
BACKGROUND & AIMS: Despite extensive investigations of portal vein thrombosis, no underlying cause is identifiable in up to 30% of patients. A recently described mutation of the prothrombin gene at nucleotide position 20210 is associated with history of venous thrombosis and was assessed in this study. METHODS: We compared the frequency of factor II G20210A and factor V G1691A (factor V Leiden) mutations in 10 patients with idiopathic portal vein thrombosis, 10 patients with nonidiopathic portal vein thrombosis, 60 patients with deep vein thrombosis of the legs, and 42 control subjects. RESULTS: The frequency of factor II G20210A mutation was increased in patients with idiopathic portal vein thrombosis (40.0%; confidence interval, 3.1%-76.9%) compared with controls (4.8%; confidence interval, 0%-11.5%) or patients with nonidiopathic portal vein thrombosis or deep vein thrombosis (P = 0.0001). In contrast, the frequency of the factor V G1691A mutation was similar in subjects with portal vein thrombosis and in controls but was increased in patients with deep vein thrombosis (P = 0.0001). CONCLUSIONS: The factor II G20210A mutation is frequent in patients with idiopathic portal vein thrombosis and should therefore be assessed under this circumstance.
Assuntos
Veia Porta/patologia , Protrombina/genética , Trombose Venosa/genética , Adulto , Idoso , Eletroforese em Gel de Poliacrilamida , Fator V/genética , Feminino , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Proteína C/metabolismo , Protrombina/metabolismoRESUMO
BACKGROUND: This investigation describes the preclinical development of a laser fiberoptic interstitial delivery system for the thermal destruction of small breast cancers. We propose adaptation of this technology to stereotactic mammographic instrumentation currently employed for diagnostic core biopsy to thermally ablate a site of disease with maximal treatment efficacy, minimal observable superficial change, reduced patient trauma, and lowered overall treatment costs. STUDY DESIGN: Laser hyperthermia is a clinical modality that seeks to achieve tumor destruction through controlled tissue heating. The advantage of laser-induced hyperthermia over traditionally used heat sources such as ultrasound, microwave, or radiowave radiation lies in the ability to focus heat localization to the specific tumor tissue site. Neodymium:yttrium aluminum garnet (Nd:YAG) laser light transmitted through a fiberoptic cable to a diffusing quartz tip can induce such temperature increases leading to localized tissue destruction. Because breast cancer occurs with greatest frequency in the mature woman whose breast tissue has undergone glandular involution with fatty replacement, this study concentrates on determining the resultant laser energy heat distribution within fat and fibrofatty tissue. This investigation studied the time-temperature responses of ex vivo human breast and porcine fibrofatty tissue, which led to an in vivo subcutaneous porcine model for the practical demonstration of a laser hyperthermia treatment of small volumes of porcine mammary chain tissue. RESULTS: Spatial recordings of the resultant temperature fields through time exhibited similar, reproducible thermal profiles in both ex vivo human breast and subcutaneous porcine fat. In vivo laser-produced temperature fields in porcine subcutaneous fat were comparable to those in the ex vivo analyses, and showed a histologically, sharply defined, and controllable volume of necrosis with no injury to adjacent tissues or to overlying skin. CONCLUSIONS: Interstitially placed, fiberoptically delivered Nd:YAG laser energy is capable of controlled tissue denaturation to a defined volume for the treatment of small breast cancers. It is hoped that this minimally invasive approach, with further investigation and refinement, may lead to the effective treatment of small, well-defined breast cancers that are commonly diagnosed through stereographic mammography and stereotactic core biopsy. The juxtaposition of such a localized treatment modality with these increasingly used diagnostic tools is of considerable promise.
Assuntos
Neoplasias da Mama/terapia , Hipertermia Induzida/métodos , Tecido Adiposo/patologia , Animais , Mama/patologia , Feminino , Tecnologia de Fibra Óptica/instrumentação , Humanos , Hipertermia Induzida/instrumentação , Terapia a Laser , Glândulas Mamárias Animais/patologia , Modelos Estruturais , Projetos Piloto , SuínosRESUMO
OBJECTIVE: To study the variations of type II soluble receptors for tumor necrosis factor (sR-TNF) in patients with systemic lupus erythematosus and investigate their use in the clinical setting. PATIENTS AND METHODS: Twenty-six patients with systemic lupus were followed for a mean 3 years. sR-TNF and other immunological parameters (C reactive protein, anti-DNA antibodies, C3 and C4 complement fractions, soluble receptors for interleukin 2) were measured in sera at different points of the disease course. The systemic lupus activity measure (SLAM) was determined at each point, and confronted with the biology results. The study was cross sectional for the group and longitudinal for the patients. RESULTS: sR-TNF was the immunological parameter which correlated best with SLAM. It also correlated with sedimentation rate, C reactive protein, thrombopenia, anemia, creatinine level, anti-DNA antibodies and sR-IL2. The longitudinal study pointed out however that this finding is not consistent for each patient. CONCLUSION: A rise in sR-TNF related to systemic lupus activity but is of limited practical interest for individual patient follow-up.
Assuntos
Lúpus Eritematoso Sistêmico/imunologia , Fator de Necrose Tumoral alfa/imunologia , Proteína C-Reativa , Seguimentos , Humanos , Estudos Longitudinais , Receptores de Interleucina-2 , SolubilidadeAssuntos
Variação Genética , Antígenos de Histocompatibilidade Classe I/genética , Alelos , Sequência de Aminoácidos , Síndrome de Behçet/genética , Linhagem Celular , Teste de Histocompatibilidade , Humanos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Homologia de Sequência de AminoácidosRESUMO
The present case report describes a 27-year-old patient who presented with post-traumatic pleural effusion. Analysis of the pleural fluid showed hypereosinophilia (990 mm-3), a decreased level of total complement, and decreased levels of C3 and C4 fractions (less than 50% of normal serum levels), indicating a local consumption mechanism for complement. Complement serum levels (CH50, C3, C4) were normal. All other aetiologic possibilities were eliminated. This case suggests that the immunopathological mechanism of post-traumatic pleural effusion may involve activation of the classical pathway of complement and a recruitment of inflammatory cells such as eosinophils.
Assuntos
Proteínas do Sistema Complemento/análise , Derrame Pleural/imunologia , Traumatismos Torácicos/imunologia , Adulto , Líquidos Corporais/imunologia , Complemento C3/análise , Complemento C4/análise , Hemólise , Humanos , Masculino , Traumatismos Torácicos/complicaçõesRESUMO
Genetic deficiencies of components of the classical pathway of complement activation are associated with an increased risk for the development of autoimmune and immune complex-mediated diseases. In the present study we report on the molecular and clinical features associated with combined heterozygous C4 and C2 deficiency in 15 individuals investigated within six families. Approximately 30% of the individuals manifested SLE or another autoimmune condition. Heterozygous C2 deficiency was related to a 28-bp deletion in the C2 gene (C2 deficiency type I), in most cases within the HLA-A25 B18 C2Q0 BfS C4A4B2 DR2 haplotype. Among 13 partial C4-deficient haplotypes transmitted, 8 carried C4A*Q0 alleles and 5 C4B*Q0 alleles. In seven cases the C4A*Q0 alleles were associated with a deletion of the C4A/CYP21P genes within the HLA-B8 C2C BfS C4AQ0B1 DR3 haplotype. In three cases, the C4B*Q0 allele was associated with a deletion of the C4B/CYP21P genes within the HLA-B18 C2C BfF1 C4A3BQ0 DR3 haplotype. In the other cases, C4A*Q0 or C4B*Q0 was dependent on as yet uncharacterized defects in the C4 gene or in C4 gene expression. In view of the relatively high frequency of heterozygous C4 deficiency in the normal Caucasian population, the expected frequency of the combined deficiency should approximate 0.001.
Assuntos
Doenças Autoimunes/imunologia , Complemento C2/deficiência , Complemento C4/deficiência , Via Clássica do Complemento/genética , Doenças do Complexo Imune/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Adulto , Doenças Autoimunes/metabolismo , Criança , Complemento C2/genética , Complemento C4/genética , Primers do DNA , Feminino , Haplótipos , Humanos , Doenças do Complexo Imune/metabolismo , Lúpus Eritematoso Sistêmico/metabolismo , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Reação em Cadeia da Polimerase , Análise de Sequência de DNARESUMO
Intramural temperatures were monitored during catheter-directed endomyocardial non-contact laser irradiation by means of an array of thermocouples inserted epicardially. Via a novel electrode-laser catheter, a total of 30 Nd-YAG laser pulses, 1064 nm, 25 W/15 s, 20 W/30 s, 15 W/45 s,n = 10 each, were aimed at various endocardial sites in the ventricles of four dogs. Temperatures increased gradually after the onset of the laser pulses. Maximum values were measured in the central area of the irradiated spots: 100 +/- 15 double daggerC at 25 W, 78+/- 23 double daggerC at 20 W and 80 +/- 13 double daggerC at 15 W. Application of 300 J of laser energy induced significantly higher temperatures at 25 W (p< 0.02) than at 20 or 15 W (20vs 15 W: p> 0.05). Initial temperature rise and lesion formation was accompanied by dwindling of local electrical potentials. There was no crater formation. Transcatheter non-contact Nd-YAG laser coagulation of healthy ventricular myocardium can be performed in a safe and controllable manner at power settings up to 20 W and laser energies up to 675 J.